SLC35F2, a Transporter Sporadically Mutated in the Untranslated Region, Promotes Growth, Migration, and Invasion of Bladder Cancer Cells

Kotolloshi, Roland; Hölzer, Martin; Gajda, Mieczysław; Grimm, Marc‐Oliver; Steinbach, Daniel

doi:10.3390/cells10010080

Cited by 13 publications

(11 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The postoperative recurrence rate of NMIBC exceeds 70%; approximately 15% of these patients progress to MIBC. The postoperative recurrence rate of patients with MIBC can exceed 50% after radical cystectomy (RC), and many patients can die from this disease ( Kotolloshi et al, 2021 ; Zhang et al, 2021 ). Because of the different prognoses and biological pathways underlying NMIBC and MIBC, a range of different treatment strategies may be required ( Nouhaud et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Signature Genes Associated With Invasiveness and the Construction of a Prognostic Model That Predicts the Overall Survival of Bladder Cancer

Liu

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

Background: Bladder cancer has become the tenth most diagnosed cancer worldwide. The prognosis has been shown to differ between non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). We aimed to identify signature genes that are associated with the invasiveness and survival of bladder cancer and to identify potential treatments.Methods: We downloaded gene expression profiles of bladder cancer from the Gene Expression Omnibus database to identify differentially expressed genes and perform weighted gene co-expression network analysis. Functional enrichment was analyzed by GO and KEGG analyses. Hub genes were identified from the significant module. Another dataset was also acquired to verify the expression of hub genes. Univariate and multivariate Cox regression analyses were applied to the dataset downloaded from The Cancer Genome Atlas database. Risk scores were calculated and the effect was evaluated by Kaplan-Meier survival analysis. A nomogram was constructed and validated using training and testing samples, respectively. Analysis of the tumor immune microenvironment was conducted with the CIBERSORT algorithm.Results: In total, 1,245 differentially expressed genes (DEGs) were identified. A distinct module was identified that was significantly correlated to invasiveness. The genes within this module were found to be significantly associated with extracellular exosomes, GTPase activity, metabolic pathways, etc. Three hub genes (VSIG2, PPFIBP2, and DENND2D) were identified as biomarkers of invasiveness; two of these (PPFIBP2 and DENND2D) were closely associated with prognosis. The risk score was regarded as an independent prognostic factor. The nomogram was associated with acceptable accuracy for predicting 1- and 5-year overall survival. The infiltrating levels of resting NK cells, activated natural killer (NK) cells, CD8+ T cells, activated memory CD4+ T cells, and T follicular helper cells, were significantly higher in the group with lower risk scores. The group with higher risk scores showed predominant infiltration by regulatory T cells (Tregs).Conclusion: We successfully identified three signature genes related to invasiveness and constructed a nomogram of bladder cancer with acceptable performance. Differences suggested by risk scores between groups of patients showing diverse patterns of immune cell infiltration may be beneficial for selecting therapeutic approaches and predicting prognosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of Signature Genes Associated With Invasiveness and the Construction of a Prognostic Model That Predicts the Overall Survival of Bladder Cancer

Liu

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…A previous study discovered a novel apoptosis-resistant pathway that promoted both immune suppression and oncogenic cell proliferation by modulating the expression of the FOXO family [ 78 ], and these are suspected to promote tumor progression. In our study, accompanied with the self-protection against apoptotic activation, a list of mRNAs including Gcm1 [ 79 ], DHRS3 [ 40 ], DUSP5 [ 80 ], NBL1 , EPN1 , SLC9A3R2 [ 81 ], SLC35F2 [ 82 ], and FOXA3 [ 83 ] involved in the cell proliferation, were significantly increased by the lactate treatment. Solute carriers (SLCs), ranking second among membrane transport proteins in terms of abundance [ 84 ], play crucial roles in human physiology through processes such as the intake of amino acids in the intestine for cell growth [ 85 ].…”

Section: Discussionmentioning

confidence: 94%

Systematic Investigations on the Metabolic and Transcriptomic Regulation of Lactate in the Human Colon Epithelial Cells

Huang

Zhou

et al. 2022

IJMS

View full text Add to dashboard Cite

Lactate, primarily produced by the gut microbiota, performs as a necessary “information transmission carrier” between the gut and the microbiota. To investigate the role of lactate in the gut epithelium cell–microbiota interactions as a metabolic signal, we performed a combinatory, global, and unbiased analysis of metabolomic and transcriptional profiling in human colon epithelial cells (Caco-2), using a lactate treatment at the physiological concentration (8 mM). The data demonstrated that most of the genes in oxidative phosphorylation were significantly downregulated in the Caco-2 cells due to lactate treatment. Consistently, the levels of fumarate, adenosine triphosphate (ATP), and creatine significantly decreased, and these are the metabolic markers of OXPHOS inhibition by mitochondria dysfunction. The one-carbon metabolism was affected and the polyol pathway was activated at the levels of gene expression and metabolic alternation. In addition, lactate significantly upregulated the expressions of genes related to self-protection against apoptosis. In conclusion, lactate participates in gut–gut microbiota communications by remodeling the metabolomic and transcriptional signatures, especially for the regulation of mitochondrial function. This work contributes comprehensive information to disclose the molecular mechanisms of lactate-mediated functions in human colon epithelial cells that can help us understand how the microbiota communicates with the intestines through the signaling molecule, lactate.

show abstract

“…Detailed methodology is given as described previously [ 40 ]. Tumor specimens were collected from bladder cancer patients at the Department of Urology, Jena University Hospital, Germany.…”

Section: Methodsmentioning

confidence: 99%

Reduced IQGAP2 Promotes Bladder Cancer through Regulation of MAPK/ERK Pathway and Cytokines

Song

Kotolloshi

Gajda

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

The progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is a major challenge in urologic oncology. However, understanding of the molecular processes remains limited. The dysregulation of IQGAP2 is becoming increasingly evident in most tumor entities, and it plays a role in multiple oncogenic pathways, so we evaluated the role of IQGAP2 in bladder cancer. IQGAP2 was downregulated in tumors compared with normal urothelium tissues and cells. IQGAP2 effectively attenuated bladder cancer cell growth independently from apoptosis. Reduced IQGAP2 promoted EMT in bladder cancer cells via activation of the MAPK/ERK pathway. In addition, IQGAP2 might influence key cellular processes, such as proliferation and metastasis, through the regulation of cytokines. In conclusion, we suggest that IQGAP2 plays a tumor-suppressing role in bladder cancer, possibly via inhibiting the MAPK/ERK pathway and reducing cytokines.

show abstract

SLC35F2, a Transporter Sporadically Mutated in the Untranslated Region, Promotes Growth, Migration, and Invasion of Bladder Cancer Cells

Cited by 13 publications

References 34 publications

Identification of Signature Genes Associated With Invasiveness and the Construction of a Prognostic Model That Predicts the Overall Survival of Bladder Cancer

Identification of Signature Genes Associated With Invasiveness and the Construction of a Prognostic Model That Predicts the Overall Survival of Bladder Cancer

Systematic Investigations on the Metabolic and Transcriptomic Regulation of Lactate in the Human Colon Epithelial Cells

Reduced IQGAP2 Promotes Bladder Cancer through Regulation of MAPK/ERK Pathway and Cytokines

Contact Info

Product

Resources

About